Interfraction interval in patients with stage III non-small-cell lung cancer treated with hyperfractionated radiation therapy with or without concurrent chemotherapy: final results in 536 patients

We investigated the influence of interfraction interval (IFI) on treatment outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT). During 3 randomized phase III and 1 phase II study, a total of 536 patients were treated with Hfx RT alone or with concurrent carboplatin/etoposide. Two hundred eighty-five patients were treated with IFI of 4.5-5.0 hours, while 251 patients were treated with IFI of 5.5-6.0 hours. "Shorter" (4.5-5.0 hours) IFI led to better overall survival (OS) (P = 0.0000) and local recurrence-free survival (LRFS) (P = 0.0000). Multivariate analyses showed IFI to be an independent prognosticator of both OS and LRFS. These results were confirmed when we separated all patients (n = 536) into those treated with Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409). Various RT-related high-grade acute toxicity was not different between the 2 IFI, but patients treated with shorter IFI had a significantly higher incidence of hematological toxicity (P = 0.002). None of the late high-grade toxicities were different between the 2 interfraction intervals. Using regression analysis, it was shown that IFI was not a significant predictor of any of acute or late high-grade (> or =3) toxicity. IFI is an important prognosticator of OS and LRFS in patients with stage III NSCLC treated with Hfx RT with or without concurrent carboplatin/etoposide. IFI led to higher incidence only of hematological toxicity, but was not predictive of any acute or late high-grade (> or =3) toxicity. A carefully designed randomized trial seems necessary to give better insight into the issue of optimal IFI in this disease.     

Influence of interfraction interval on local tumor control in patients with limited-disease small-cell lung cancer treated with radiochemotherapy

PURPOSE: To investigate the influence of interfraction interval (IFI) on local recurrence-free survival (LRFS) in patients with limited-disease small-cell lung cancer (LD SCLC) treated with accelerated hyperfractionated radiotherapy (Acc Hfx RT) and concurrent cisplatin and etoposide (PE). METHODS AND MATERIALS: A total of 103 patients were treated with either "early" (Cycle 1) or "late" (Cycle 4) concurrent Acc Hfx RT/PE. Two daily fractions were nonrandomly given using an IFI of either 4.5-5.0 h ("shorter") (n = 52) or 5.5-6.0 h ("longer") (n = 51). RESULTS: The median LRFS and 5-year LRFS rate for all 103 patients were 52 months and 48%, respectively. Besides gender, Karnofsky performance status, and treatment group, IFI also influenced LRFS, whereas age and weight loss did not. When a multivariate model was used, IFI was marginally insignificant (p = 0.0770) as a predictor of LRFS. In terms of individual treatment groups, IFI was not significant in "early" Acc Hfx RT/PE but showed a strong trend in a "late" Acc Hfx RT/PE regimen. Although a shorter IFI led to a higher incidence of high-grade (>or=3) esophagitis, leukopenia, and infection, a correlation analysis of toxicities with all potential prognostic factors showed that a shorter IFI was not an independent predictor of any acute high-grade toxicity. CONCLUSION: "Shorter" IFI had a marginally insignificant influence on LRFS. A strong trend favoring it was observed in patients treated with "late" concurrent Acc Hfx RT/PE. This may be of interest because it could contribute to further understanding of potential biologic parameters influencing treatment outcome.     

Radiotherapy alone versus radiochemotherapy in patients with stage IIIA adenocarcinoma (ADC) of the lung

Purpose

To evaluate the outcome of radiotherapy (RT) versus radiochemotherapy (RT-CHT) in patients with locally advanced (stage III) inoperable adenocarcinoma of the lung.

Patients and methods

146 patients with these characteristics were among 600 patients enrolled into five prospective trials and were treated with either hyperfractionated (Hfx) RT (64.8 and 69.6 Gy using 1.2 Gy bid) alone (n = 33) or with Hfx RT (64.8 and 69.6 Gy using 1.2 Gy bid and 67.6 Gy using 1.3 Gy bid) and concurrent carboplatin–etoposide or paclitaxel–carboplatin (n = 113).

Results

The median times and 5-year overall survival (OS), local progression-free survival (LPFS) and the distant metastasis-free survival (DMFS) rates for all 146 patients were 17, 20 and 20 months, respectively, and 15, 26 and 33, respectively. RT-CHT was superior to RT alone in terms of both OS (MST 19 vs. 12 months, respectively, 5-year OS 18 vs. 6 %, respectively; p = 0.003) and LPFS (MTLP 21 vs. 15 months, respectively, 5-year LPFS 28 vs. 0 %; p = 0.06), but not the DMFS (p = 0.43). In all 146 patients, the most frequent acute high-grade toxicity was esophageal, bronchopulmonary and hematological (each 12 %), while the most frequent late high-grade toxicity was bronchopulmonary (4 %) and esophageal (3 %). RT-CHT caused significantly more frequent acute high-grade (>3) esophageal (15 %), and hematological (15 %), while late high-grade toxicity was similar between RT and RT-CHT groups of patients.

Conclusion

RT-CHT achieved excellent results (MST 19 months, 5-year survival 18 %) in this patient population accompanied with low toxicity, comparing favorably to results of other similar studies.     

Stage III non-small-cell lung cancer treated with high-dose hyperfractionated radiation therapy and concurrent low-dose daily chemotherapy with or without weekend chemotherapy: retrospective analysis of 301 patients

We investigated the outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with high-dose hyperfractionated radiation therapy (Hfx RT) and concurrent chemotherapy (CHT) consisting of carboplatin (C) and etoposide (E). During three prospective randomized phase III and one prospective phase II study enrolling a total of 536 patients, 301 patients were treated with high-dose Hfx RT (69.6 Gy) and either low-dose daily CE (50 mg each) (n = 163) or daily CE (30 mg each) accompanied by "weekend" CE (100 mg of each on Saturdays and Sundays) (n = 138). The median survival time for all 301 patients is 22 months and 5-year survival is 24%. Median local recurrence-free survival (LRFS) time is 21 months and 5-year local recurrence-free survival is 32%. The median time to distant metastasis is 25 months, and 5-year distant metastasis-free survival (DMFS) is 35%. Only the type/schedule of CHT administration did not influence overall survival, LRFS, and DMFS. On multivariate analyses using these three endpoints, age stage, interfraction interval, and type/schedule of CHT administration did not predict survival, LRFS, and DMFS, while gender, KPS, and weight loss did. Only high grade hematologic toxicity was more frequent in weekend CHT group. High dose Hfx RT and concurrent low-dose daily CE with or without weekend CE is an active treatment approach in stage III NSCLC that led to high overall survival, LRFS, and DMFS rates.     

不同放化疗组合方案对广泛期SCLC预后影响

目的 探讨不同放化疗组合方案对广泛期SCLC预后的影响。方法 回顾分析2011—2015年收治的322例广泛期SCLC患者,均接受依托泊苷+顺铂或卡铂标准方案化疗;根据RECIST标准将化疗后疗效分为CR、PR、SD、PD,排除化疗后进展的90例,共入组232例。根据化疗有效后是否行放疗将患者分为放疗组(187例)和无放疗组(45例)。根据放疗的早晚分为早放疗组(化疗≤3个周期接受放疗,65例)和晚放疗组(化疗>3个周期接受放疗,122例)。根据放疗和化疗顺序分为同步放化疗组(45例)和序贯放化疗组(142例)。Kaplan-Meier计算生存率,Logrank检验差异,Cox模型多因素预后分析。结果 中位OS、PFS、LRFS全组分别为13.2、 8.7、14.6个月;无放疗组分别为 8.7、5.6、5.9个月,有放疗组分别为15.0、9.8、19.2个月(P=0.00、0.00、0.00);早放疗组分别15.4、8.0、19.2个月,晚放疗组分别为14.6、10.8、18.1个月(P=0.720、0.426、0.981);同步放化疗组分别为19.4、10.8、19.8个月,序贯放化疗组分别为13.8、9.8、17.8个月(P=0.036、0.656、0.768)。接受放疗患者不良反应较无放疗患者增加(P=0.038),但≥3级严重不良反应相似(P=0.126)。     

Toxicity of concurrent hyperfractionated radiation therapy and chemotherapy in locally advanced (stage III) non-small cell lung cancer (NSCLC): single institution experience in 600 patients

Purpose

to investigate toxicity of hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT) in patients with locally advanced non-small cell lung cancer (NSCLC) and factors independently influencing it.

Materials and methods

Of a total of 600 patients treated during five prospective studies Hfx RT alone was given in 127 and Hfx RT-CHT was given in 473 patients. Hfx RT doses were 64.8 and 69.6?Gy (1.2?Gy bid) and 67.6?Gy (1.3?Gy bid). CHT administration consisted of concurrent carboplatin and etoposide in 409 patients and concurrent carboplatin and paclitaxel in 64 patients.

Results

Acute oesophageal toxicity was significantly increased with concurrent CHT (p?=?0.034), as well as bronchopulmonary (p?=?0.044) and haematological toxicity (p?p?=?0.007) toxicity was significantly more frequent in the RT-CHT group. Only acute high-grade haematological toxicity was significantly more frequent in split CHT than in daily CHT and Hfx RT alone (p?Conclusions This study reconfirmed low acute and late high-grade toxicity in stage III NSCLC treated with concurrent RT-CHT and identified factors influencing it.     

Involved-field radiotherapy is effective for patients 70 years old or more with early stage non-small cell lung cancer.

BACKGROUND AND PURPOSE: Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers, especially in patients 70 years old or more. In this study, we investigated the efficacy and safety of involved-field radiotherapy (IFRT) for patients 70 years old or more with early stage NSCLC. PATIENTS AND METHODS: We conducted a multicenter prospective study in elderly patients with NSCLC treated with intensity-modulated radiotherapy (IMRT). From January 1999 to December 2001, 80 patients with medically inoperable or refused surgery early stage (I/II) NSCLC were eligible for toxicity and treatment response analysis. IMRT plans were designed to deliver 66.6 Gy to involved-field that included only the primary tumor and clinically enlarged lymph nodes using six equidistant coplanar 6-MV beams. Elective nodal failure (ENF) was defined as a recurrence in an initially uninvolved lymph node in the absence of local failure. RESULTS: The objective response rate of all patients was 88.6% with a median overall survival (OS) time of 38 months and the 1-, 2- and 5-year OS rates and local progression-free survival (LPFS) rates were 65.8%, 55.7%, 25.3% and 84.8%, 59.5%, 34.2%, respectively. The medians OS time for patients with gross tumor volume (GTV) >100.8 cm3 and GTV < or =100.8 cm3 were 13 and 50 months, respectively (p=0.0001). Only 29 patients (36.7%) with ENF were identified, with a median time to treatment failure of 55 months (range, 49-61 months) after treatment. There were no treatment-related deaths or grade 4 toxicity. Grade 3 toxicities were esophagitis (1.3%), radiation pneumonitis (3.8%) and hematological effects (2.5%). CONCLUSIONS: This study indicated that IFRT using IMRT did not cause a significant amount of failure in lymph node regions not included in the tumor volume and improved outcomes in elderly patients. Therefore, IFRT is an acceptable technique in the treatment of elderly inoperable NSCLC.     

Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial.

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m(2)) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P =.0075). It also offered higher progression-free survival (46% v 25% at 5 years; P =.0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P =.041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P =.0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.     

老年广泛期小细胞肺癌放疗价值研究

目的 探讨胸部放疗(TRT)对老年广泛期小细胞肺癌(ES-SCLC)患者预后的影响。方法 回顾分析天津医科大学肿瘤医院2010-2016年收治的83例≥65岁转移性ES-SCLC患者,所有入组患者均接受依托泊苷联合顺铂或卡铂标准方案化疗。经PSM倾向评分匹配有无TRT各入组35例。男56例、女14例,年龄65~85岁(中位数69岁),化疗1~11个周期(中位数4个周期),胸部照射剂量30~60 Gy (中位数50 Gy)。观察终点为总生存(OS)、无进展生存(PFS)、局部无复发生存(LRFS)。采用Kaplan-Meier方法计算生存率,Logrank比较组间差异,Cox回归模型多因素预后分析。结果 全组患者1年OS、PFS、LRFS率分别为40%、16%、21%;有无TRT患者的1年OS率分别为52%和29%(P=0.005),1年PFS率分别为30%和3%(P<0.001),1年LRFS率分别为38%和6%(P<0.001)。接受TRT并未增加患者不良反应的发生率(P=0.690)。结论 老年ES-SCLC患者加用TRT能够明显提高胸部肿瘤控制率,延长患者生存期,值得进一步进行大样本前瞻性研究证实。     

老年局部晚期食管癌同步放化疗与单纯放疗的疗效比较

目的：比较老年局部晚期食管癌患者采用同步放化疗（CRT）和单纯放疗（RT）的疗效和急性不良反应。方法：回顾性分析2010年1月—2016年1月于河北医科大学第四医院就诊,年龄>70岁的82例老年局部晚期食管癌患者。比较CRT和RT两个治疗组间的完全缓解率（CRR）、部分缓解率（PRR）、疾病缓解率（DCR）、无进展生存期（PFS）、总生存期（OS）和急性不良反应,并分析食管癌预后的影响因素。结果：CRT组患者的CRR （33.3%）明显高于RT组（14.5%,P=0.049）,两组之间PRR和DCR的差异无统计学意义（P=0.058,0.064）。CRT组患者的中位PFS及PFS≥1、2、3年的患者比例均显著高于RT组（P=0.007）。CRT组患者的中位OS及OS≥1、2、3年的患者比例亦显著高于RT组（P=0.012）。单因素分析显示不同治疗方案、CRR是PFS和OS的影响因素。多因素分析显示CRR为PFS的独立预后影响因素,不同治疗方案、CRR是OS的独立预后影响因素（均为P <0.05）。CRT组患者的部分急性不良反应有恶心、呕吐、白细胞减少症、血小板减少症,发生率均高于RT组（均为P <0.05）。结论：同步放化疗可作为老年局部晚期食管鳞癌患者的治疗方案,且疗效优于单纯放疗,但仍需密切关注患者的不良反应。     

Hyperfractionated radiation therapy and concurrent low-dose, daily carboplatin/etoposide with or without weekend carboplatin/etoposide chemotherapy in stage III non-small-cell lung cancer: a randomized trial

PURPOSE: To investigate whether the addition of weekend chemotherapy consisting of carboplatin/etoposide to hyperfractionated radiation therapy (Hfx RT) and concurrent daily carboplatin/etoposide offers an advantage over the same Hfx RT/daily carboplatin/etoposide. METHODS AND MATERIALS: A total of 195 patients (Group I, 98; Group II, 97) were treated with either Hfx RT to a total tumor dose of 69.6 Gy via 1.2 Gy b.i.d. fractionation and daily 50 mg each of carboplatin and etoposide during the RT course (Group I) or the same Hfx RT with daily carboplatin/etoposide consisting of 30 mg each of carboplatin and etoposide and with weekend (Saturdays and Sundays) 100 mg each of carboplatin and etoposide during the RT course (Group II). RESULTS: No difference was found regarding median survival time and 5-year survival rates (20 vs. 22 months and 20% vs. 23%; p = 0.57). Median time to local progression was 20 and 19 months, respectively, while 5-year local progression-free survival rates were 28% and 27%, respectively (p = 0.66). Also, there was no difference regarding either median time to distant metastasis and 5-year distant metastasis-free survival (21 vs. 25 months and 29% vs. 34%, p = 0.29). There was no difference in the incidence of various nonhematologic toxicities between the two treatment groups, but patients treated with the weekend CHT had significantly more high-grade (> or = 3) hematologic toxicity (p = 0.0046). Late high-grade toxicity was not different between the two treatment groups. CONCLUSION: The addition of weekend carboplatin/etoposide did not improve results over those obtained with Hfx RT and concurrent low-dose, daily carboplatin/etoposide, but it led to a higher incidence of acute high-grade hematologic toxicity.     

T1-2N1M0期鼻咽癌IMRT同期化疗疗效分析

目的 回顾性成组配对分析早期鼻咽癌单纯IMRT与IMRT同期化疗疗效及不良反应。方法 2009—2010年共98例T_1-2N₁M₀期鼻咽癌患者行单纯放疗或同期放化疗,筛选出39对患者进行疗效及不良反应对比分析。Kaplan-Meier法计算生存率且Logrank法检验。结果 3年随访率为95%。单纯IMRT组和同期放化疗组3年OS率分别为97%、95%(P=0.411),PFS率分别为97%、92%(P=0.301),LRFS率分别为97%、97%(P=0.606),DMFS率分别为100%、92%(P=0.082)。白细胞减少、贫血、血小板减少发生率同期放化疗组大于单纯IMRT组(P=0.000、0.000、0.000),单纯IMRT组与同期放化疗组3级口腔口咽黏膜炎发生率分别为26%和36%(P=0.093),听力下降发生率分别为41%、62%(P=0.100)。结论 同期化疗联合IMRT未能提高早期鼻咽癌T_1-2N₁期患者OS、PFS、LRFS率,亦未能降低DMFS率;且血液毒性、3级黏膜炎、听力下降发生率较单纯IMRT组高。     

Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin/paclitaxel in patients with early-stage (I/II) non-small-cell lung cancer: long-term results of a phase II study.

PURPOSE: Feasibility and activity of concurrent hyperfractionated radiotherapy (Hfx RT) and low-dose, daily carboplatin and paclitaxel were investigated in patients with early-stage (I/II) non-small-cell lung cancer in a phase II study. PATIENTS AND METHODS: Fifty-six patients started their treatment on day 1 with 30 mg/m2 of paclitaxel. Hfx RT using 1.3 Gy bid to a total dose of 67.6 Gy and concurrent low-dose daily carboplatin 25 mg/m2 and paclitaxel 10 mg/m2, both given Mondays through Fridays during the RT course, started from the second day. RESULTS: There were 29 complete responses (52%) and 15 partial responses (27%), and 12 patients (21%), experienced stable disease. The median survival time was 35 months, and 3- and 5-year survival rates were 50% and 36%, respectively. The median time to local progression has not been achieved, but 3- and 5-year local progression-free survival rates were 56% and 54%, respectively. The median time to distant metastasis has not been achieved, but 3- and 5- year distant metastasis-free survival rates were 61% and 61%, respectively. The median and 5-year cause-specific survivals were 39 months and 43%, respectively. Acute high-grade (> 3) toxicity was hematologic (22%), esophageal (7%), or bronchopulmonary (7%). No grade 5 toxicity was observed. Late high-grade toxicity was rarely observed (total, 10%). CONCLUSION: Hfx RT and concurrent low-dose daily carboplatin/paclitaxel was feasible with low toxicity and effective in patients with stage I/II non-small-cell lung cancer. It should continue to be investigated for this disease.     

胸段食管鳞癌诱导化疗联合同期放化疗对比同期放化疗的配对分析

目的 比较不能手术胸段食管鳞癌诱导化疗联合同期放化疗对比同期放化疗的疗效差异。方法 回顾性分析2002-2015年接受根治性放化疗的胸段食管鳞癌患者 267例,化疗均采用多西他赛联合顺铂方案。以年龄、性别、PS评分、肿瘤部位、肿瘤长度、TNM分期作为配对因素,将 85例接受诱导化疗联合同期放化疗的患者作为研究组与接受单纯同期放化疗的患者1∶1配对,比较两组的临床疗效和毒性差异。采用Kaplan-Meier法进行生存分析,Logrank检验进行组内分析,Cox回归模型进行多因素分析。结果 170例患者的中位随访时间为18(3~72)个月。放化疗后诱导组、同期组的客观缓解率分别为74.1%、58.8%(P=0.035),3年总生存率分别为44.2%、 29.7%(P=0.028),3年无进展生存率分别为34.8%、 15.4%(P=0.015)。亚组分析显示诱导化疗有效组总生存率、无进展生存率和无局部区域复发生存率高于诱导化疗无效组(P=0.002、0.001、0.002),两组无远处转移生存率相近(P=0.116)。诱导组≥3级白细胞下降的发生率显著高于同期组(38.8%∶24.7%,P=0.048)。多因素分析显示年龄、是否采用诱导化疗是影响总生存的因素(P=0.003、0.016)。结论 与同期放化疗相比,诱导化疗联合同期放化疗可获得较好的近期疗效并可延长食管鳞癌患者的生存。诱导组血液学毒性的发生率较高但可耐受,值得进一步开展前瞻性对照研究以确证其有效性。     

局部晚期鼻咽癌IMRT联合化疗±靶向治疗疗效与安全性对比

目的 回顾对比局部晚期鼻咽癌患者IMRT联合化疗±靶向治疗的疗效与不良反应,初步评价放化疗基础上加用靶向药物的必要性。方法 收集2007—2012年间接受IMRT联合同步化疗±辅助化疗加靶向治疗的Ⅲ—Ⅳ_{b期鼻咽癌患者42例(试验组),同期仅行IMRT联合同步放化疗±辅助化疗的患者与其按1∶4配对入组168例(对照组)。Kaplan-Meier法计算生存率并Logrank检验差异,余用χ²检验。结果 随访率为100%,试验组、对照组3年样本量分别为42例、168例。试验组3年OS、LRFS、DMFS率分别为94%、100%、92%,对照组的分别为87.3%、94.6%、89.1%(P=0.647、0.193、0.744)。3—4级胃肠道不良反应、骨髓抑制及口腔黏膜反应发生率试验组分别为7%(3/42)、26%(11/42)、41%(17/42),对照组分别为3.6%(6/168)、17.3%(29/168)、14.9%(25/168)(P=0.388、0.272、0.000)。结论 初步结果提示IMRT联合化疗的基础上加用靶向治疗对提高局部晚期鼻咽癌患者OS、LRFS及DMFS的疗效不明显,且有可能加重放化疗相关的口腔黏膜反应。}     

乳腺导管原位癌的单中心预后分析

背景与目的:目前中国乳腺导管原位癌(ductal carcinoma in situ,DCIS)的发病率逐年升高,而现有治疗策略主要基于欧美大型随机对照研究.探索中国人群中DCIS患者的临床特征、复发模式和预后影响因素,以便优化临床决策.方法:回顾性分析2008年1月—2017年1月复旦大学附属肿瘤医院收治的1185例...     

放射治疗对初诊转移性头颈鳞癌预后的影响

目的 基于美国SEER数据库的资料,评估放疗对初诊转移性头颈鳞癌（HNSCC）患者预后的影响。方法 利用SEER数据库筛选2010—2015年初诊为转移性HNSCC的患者1226例,包括放疗组762例（62.1%）,未放疗组464例（37.9%）。采用Kaplan‐Meier法计算癌症特异性生存（CSS）和总生存（OS）,在全组患者中通过Cox多因素回归和倾向配比评分（PSM）评估放疗对预后的影响。依据多因素分析结果将患者分为低、中和高风险组,并在不同风险组中分析放疗对生存的影响。结果 全组患者中位CSS和OS时间分别为11.0个月和10.0个月;放疗组和未放疗组的中位CSS时间分别为13.0个月和6.0个月,中位OS时间分别为12.0个月和6.0个月。多因素分析显示年龄、原发灶部位、T分期、N分期、转移脏器个数、手术、放疗和化疗是独立的预后影响因素（CSS：P值为0.045、0.021、0.001、0.002、<0.001、<0.001、<0.001、<0.001;OS：P值为0.002、<0.001、0.002、<0.001、<0.001、<0.001、<0.001、<0.001）。PSM配对后,在低、中、高风险组中,放疗和未放疗患者3年CSS分别为：62.5%∶23.5%、22.4%∶15.7%和10.5%∶9.6%（P=0.008、0.001、0.203）;3年OS分别为：58.0%∶20.8%、19.8%∶12.7%和7.0%∶6.1%（P=0.002、0.001、0.166）。结论 放疗显著提高低风险和中风险组患者的CSS和OS,但高风险组患者不能从放疗中生存获益。     

经匹配后放化疗与手术治疗局限期小细胞肺癌预后比较

目的 比较手术与放化疗治疗局限期小细胞肺癌(SCLC)患者的总生存(OS)、无进展生存(PFS)、颅内无进展生存(BMFS)预后差异。方法 收集2000-2016年在浙江省肿瘤医院经手术治疗的局限期SCLC患者 69例,在 503例经根治性放化疗的局限期SCLC数据库中,按照T、N分期,治疗年份,年龄,性别,是否预防性脑照射(PCI)等进行1∶1匹配 69例患者为放化疗组。结果 共纳入 138例患者,手术组 69例(Ⅰ期 24例、Ⅱ期 14例、Ⅲ期 31例),放化疗组 69例(Ⅰ期 24例、Ⅱ期 14例、Ⅲ期 31例)。手术组与放化疗组的中位OS期分别为37.1个月(95%CI为 24.1~50.2个月)和45.0个月(95%CI为 15.8~74.2个月),2、5年OS率分别为60%、45%和64%、45%(P=0.846);中位PFS期分别为27.1个月(95%CI为 0.00~60.3个月)和36.2个月(95%CI为 20.9~51.4个月),2、5年PFS率分别为52%、38%和56%、40%(P=0.610)。2、5年BMFS率分别为80%、76%和84%、80%(P=0.774)。Ⅰ期手术组、放疗组 5年OS率分别为62%、40%(P=0.038),PFS率分别为80%、40%(P=0.048),BMFS率分别为92%、95%(P=0.816)。Ⅱ期手术组、放化疗组 5年OS率分别为41%、51%(P=0.946),PFS率分别为65%、42%(P=0.280),BMFS率分别为75%、78%(P=0.720)。Ⅲ期手术组、放化疗组 5年OS率分别为25%、48%(P=0.220),5年PFS率分别为28%、36%(P=0.333),5年BMFS率分别为76%、74%(P=0.842)。结论 手术治疗可为Ⅰ期患者带来生存获益,Ⅱ期患者两组生存相当,Ⅲ期患者放化疗组有更好生存趋势。最终结论需要更大样本或开展前瞻性研究得出。     

肝癌伴抑郁患者血清CRP、hs-CRP水平变化及其对预后的影响

目的 探讨抑郁对肝癌肝切除患者血清C反应蛋白(CRP)、超敏C反应蛋白(hs-CRP)水平及预后的影响。方法 纳入肝癌行肝切除术患者251例,术前3天使用医院焦虑抑郁量表-抑郁亚量表(Hospital anxiety and depression scale,HADS-D)、9条目患者健康问卷(9-item patients health questionnaire,PHQ9)对患者进行抑郁评估,根据评分结果将患者分为抑郁组(n=95)和无抑郁组(n=156),比较两组患者术前血清CRP、hs-CRP、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,生存分析Kaplan-Meier法比较两组患者术后无瘤生存期(DFS)和总生存期(OS)。结果 抑郁组患者的血清CRP、hs-CRP、ALT、AST水平均高于无抑郁组(P＜0.05)。随访3.5年结果显示,164例(抑郁组65例,无抑郁组99例)患者出现复发或转移、47例(抑郁组22例,无抑郁组25例)死亡,抑郁组患者DFS、OS均显著低于无抑郁组(P＜0.05)。多因素Cox回归分析显分析显示,肝功能分级、BCLC分期、抑郁是影响肝癌预后的独立危险因素。Spearman相关分析显示,患者抑郁程度与血清CRP、hs-CRP水平呈正相关(P＜0.05),DFS、OS与血清CRP、hs-CRP水平呈负相关(P＜0.05)。结论 抑郁可能介导血清CRP、hs-CRP水平升高,维持患者体内的炎症反应,导致肝功能损伤加重,ALT、AST水平升高,进而对肝癌患者预后造成不良影响。     

Radiation dose >=54 Gy and CA 19--9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

ABSTRACT: BACKGROUND: Unresectable pancreatic cancer (UPC) has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease is becoming clinically important. We investigated whether the radiation dose used in chemoradiation (CRT) as definitive treatment for UPC and the CA 19--9 response to therapy have an impact on overall survival (OS). METHODS: From 1997--2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy). All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other) and 24 received adjuvant chemotherapy. RESULTS: 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy). Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis minimum CA 19--9 post-CRT of <90 U/mL was favorably associated with OS (12.3 versus 8.8 months, p = 0.012). Radiotherapy dose >=54 Gy trended towards improved OS (11.3 versus 6.8 months, p = 0.089). By multivariable analysis a delivered RT dose of >=54 Gy (HR 0.47, p = 0.028) and minimum CA 19--9 post-CRT of <90 U/mL (HR 0.35, p = 0.008) were associated with OS. CONCLUSIONS: CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to >=54 Gy or who experienced a minimum post-CRT CA 19--9 <90 U/mL had improved likelihood of long-term survival.